Viral diseases are the most common infectious diseases, and have become global public health problems due to their features of highly infectivity and high variability. The targets of the existing antiviral drugs are mostly viral enzymes. Viral enzyme inhibitors drugs have advantages such as explicit targets, high specificity, and strong efficacy, but also apparent shortages of narrow antiviral spectrum, and problem of drug resistance leaded by the tends of the high variability of the viruses. The emerging of the new virus variants and unknown viruses make existing antiviral drugs, which have frequent problems of drug resistance, powerless. Therefore, the development of new antiviral drugs is imminent. Hepatitis C virus (HCV) infected about 200 million people in the entire world, wherein there are about 40 million HCV carriers in China. HCV is highly infectious. Once infected by HCV, it is difficult to spontaneously clear the viruses. 80% of those infected will become chronic hepatitis C (CHC). If no antiviral treatment is properly and timely received, 20-30% of patients with CHC will develop cirrhosis 20-30 years after the infection, and epidemiological studies have shown that chronic HCV infection is closely associated with primary liver cancer. There is no effective vaccine to prevent this infection. The combination of pegylated interferon α (PEG-IFN-α) and ribavirin (RBV) is current standard therapy for the treatment of chronic HCV infection, but this standard therapy has defects of significant side effects of toxicity and a long treatment course, so its clinical application has some limitations. In recent years, the rapid development of biology leads to a breakthrough understanding for people in terms of HCV infection and replication. Pharmaceutical companies developed a variety of HCV-specific antiviral drugs which act directly on the virus (DAAs). Recently, a new target treatment regimen without interferon has been proposed in the field of anti-HCV drug research. The new target treatment is similar to HIV cocktail therapy, and is formed by the combination of HCV inhibitor drugs with multiple action mechanisms, and ultimately treatment without interferon formed by the combination of a variety of small molecule inhibitors is promising. The ideal treatment regimen can block viral replication in many processes simultaneously, and help delaying drug resistance, but still needs research discoveries on novel HCV inhibitors with different mechanism of action as a basis.
The inventors found and confirmed that a group of benzamide compounds with broad spectrum inhibition of viral activity during the early screening study of antiviral drugs with host cell factor APOBEC3G as targets. Such compounds also significantly inhibit HCV replication, but have poor metabolic stability, and low bioavailability. When conducting structural optimization studies, the inventors discovered and confirmed that a new class of substituted aryl cyanides had better inhibitory activity on HCV replication and pharmaceutical properties had been improved significantly. Furthermore, the compounds of the present invention may play a broad-spectrum antiviral role on the basis of the new cellular mechanisms. The compounds of the invention and its role are not reported by relevant literature domestically and abroad to date.